Structure-guided design of CPPC-paired disulfide-rich peptide libraries for ligand and drug discovery
Yapei Wu, Shihui Fan, Dong Meng, Jinjing Li, Chuilian Kong, Jie Zhuang, Xiaoting Meng, Shuaimin Lu, Yibing Zhao, Chuanliu Wu
Abstract
, CPPC-DRPs). A range of new CPPC-DRPs were designed or selected from either random or structure-convergent peptide libraries. Thus, for the first time we revealed that the CPPC-DRPs can maintain diverse 3D structures by taking advantage of constraints from unique dimeric CPPC mini-loops, including irregular structures and regular α-helix and β-sheet folds. New CPPC-DRPs that can specifically bind the receptors (CD28) on the cell surface were also successfully discovered and identified using our DRP-discovery platform. Overall, this study provides the basis for accessing an unconventional peptide structure space previously inaccessible by natural DRPs and computational designs, inspiring the development of new peptide ligands and therapeutics.